Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (n=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14–19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14–21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p < 0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p < 0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.
Animals ; Antihypertensive Agents ; Arterial Pressure ; Blood Pressure ; Catalase ; Female ; Hypertension ; Hypertension, Pregnancy-Induced* ; Maternal Mortality ; Models, Animal* ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Oxidative Stress* ; Pre-Eclampsia ; Pregnancy ; Punicaceae ; Rats* ; Tyrosine ; Vascular Endothelial Growth Factor A

Spontaneous hepatic rupture, which is a complication of hypertension in pregnancy, is extremely rare. However, high maternal and perinatal mortality rates are observed. Several factors, namely, age over 30 years, multiparity, severe preeclampsia, or HELLP syndrome (a group of symptoms which include hemolytic anemia, hepatic enzyme increase, and thrombocytopenia), are associated with this condition. An autopsy case of a woman with twin pregnancy was studied. She was at 36 weeks of gestational age and suffered from the sudden development and rapid progression of hypertension. Moreover, she died because of spontaneous hepatic rupture despite an emergency operation. Autopsy revealed a capsular rupture of the right lobe of the liver with numerous blood clots and hypovolemic signs, such as weak postmortem lividity and palor of the skin and conjunctiva. A close examination of the trunk and liver for the classification of the cause of rupture and an assessment of medical history, such as preeclampsia, are needed during postmortem examination of pregnant women with hepatic rupture or her fetus. To the best of our knowledge, this fatal complication in pregnant women is not yet presented in postmortem examinations in Korea. Thus, we report the findings of this case to share the knowledge.
Anemia, Hemolytic ; Autopsy* ; Classification ; Conjunctiva ; Emergencies ; Female ; Fetus ; Gestational Age ; HELLP Syndrome ; Humans ; Hypertension ; Hypertension, Pregnancy-Induced ; Hypovolemia ; Korea ; Liver ; Parity ; Perinatal Mortality ; Pre-Eclampsia* ; Pregnancy ; Pregnancy, Twin ; Pregnant Women* ; Rupture* ; Rupture, Spontaneous ; Skin

Pre-eclampsia is known to cause considerable maternal morbidity and mortality. Thus, many studies have examined the etiopathogenesis of pre-eclampsia. While many pathophysiological factors related to pre-eclampsia have been identified, the precise etiopathogenesis of pre-eclampsia remains unclear. Numerous studies have identified factors for the early prediction for pre-eclampsia to lead to preparation and closer observation on pre-eclampsia when it occurs. This article reviews on current studies of biomarkers and genetic factors related to pre-eclampsia, which may be important for developing strategies for early prediction of pre-eclampsia.
Biomarkers* ; Early Diagnosis ; Mortality ; Pre-Eclampsia*

Hypertension is the most common medical disorder encountered in pregnancy, complicating 5% to 10% of all pregnancies. It is a major cause of maternal, fetal and newborn morbidity and mortality, increasing the risk of cerebrovascular events, organ failure and placenta abruptio in mothers and the risk of intrauterine growth restriction, prematurity and intrauterine death in fetuses. There are four types of hypertensive disorders in pregnancy: gestational hypertension, preeclampsia and eclampsia syndrome, chronic hypertension of any etiology, and Preeclampsia superimposed on chronic hypertension. The decision to treat hypertension in pregnancy should consider the benefit-harm balance for both mother and fetus, and depends on gestational age, blood pressure levels, and presence of preeclampsia. As termination of pregnancy is the only cure for preeclampsia, there is general agreement that delivery rather than observation is suggested in women with severe preeclampsia, eclampsia, or mild hypertension at term. However, it is not clear whether women with mild hypertension at near term can be managed expectantly as well as whether antihypertensive therapy for mild to moderate hypertension should be initiated. In 2013, the American College of Obstetricians and Gynecologists provided evidence-based recommendations for the management of patients with hypertension during and after pregnancy, but it concluded that the final decision should be individualized and made by the health care provider and patient in all instances. Therefore, well-designed large trials are needed to clarify the indication for antihypertensive use and the selected population who would benefit from expectant management for mild to moderate hypertension at preterm.
Blood Pressure ; Disease Management ; Eclampsia ; Female ; Fetus ; Gestational Age ; Health Personnel ; Humans ; Hypertension* ; Hypertension, Pregnancy-Induced ; Infant, Newborn ; Mortality ; Mothers ; Placenta ; Pre-Eclampsia ; Pregnancy*

Pregnancy-related venous thromboembolism (VTE) is one of the leading causes of maternal morbidity and mortality, developed in the antenatal and postpartum periods of pregnancy. The incidence of VTE during normal pregnancy is four- to six-fold higher than in the general reproductive aged female population. Physiologic changes such as hypercoagulable state, decreased venous capacitance, and reduced venous blood flow due to mechanical obstruction from gravid uterus compromise this condition. The prominent risk factors for VTE are thrombophilia, history of circulatory disease and previous VTE, preeclampsia and related disorders, and Cesarean section. In case of suspicion of VTE, prompt diagnosis and management are needed with the caution of potential adverse effects on the fetus. Low molecular weight heparin treatment is preferred due to better safety, more consistent bioavailability, ease of administration, lower risk of drug-related osteoporosis and thrombocytopenia and easier monitoring. For pregnant women with acute VTE, adjusted-dose subcutaneous low molecular weight heparin should be administrated antenatally and continued for at least 6 weeks postpartum. For prevention of VTE, mechanical prophylaxis such as physiotherapy, exercise, compression stockings, and intermittent pneumatic compression devices could be used. Thromboprophylaxis should also be considered for pregnant subjects with certain risks such as carriers of molecular thrombophilia or previously experienced VTE.
Biological Availability ; Cesarean Section ; Diagnosis ; Female ; Fetus ; Heparin, Low-Molecular-Weight ; Humans ; Incidence ; Intermittent Pneumatic Compression Devices ; Mortality ; Osteoporosis ; Postpartum Period ; Pre-Eclampsia ; Pregnancy* ; Pregnant Women ; Risk Factors ; Stockings, Compression ; Thrombocytopenia ; Thromboembolism* ; Thrombophilia ; Uterus ; Venous Thromboembolism

Preeclampsia is one of the most common complications of pregnancy that is prevalent worldwide, resulting in substantial maternal and neonatal morbidity and mortality. Although the cause remains unclear, preeclampsia may be initiated by abnormal placentation and reduced placental perfusion, followed by an imbalance of angiogenic and antiangiogenic factors and subsequent systemic endothelial dysfunction. High level of antiangiogenic factors, such as soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR-1, also known as sFlt-1) and soluble endoglin, and low levels of angiogenic factors, such as free maternal VEGF and placental growth factor (PlGF), are associated with preeclampsia. Angiogenic and antiangiogenic factors also play an important role during lung angiogenesis, and an imbalance between the two types of factors triggered by inflammation disrupts angiogenesis in bronchopulmonary dysplasia (BPD). Because preeclampsia represents an antiangiogenic state, preterm infants born to mothers with preeclampsia would be at increased risk of developing BPD due to impaired lung development. Recently, preeclampsia has been shown to be independently associated with a high risk for BPD. I have reviewed recent progress in research concerning the correlation between preeclampsia and BPD in aspect of pathophysiology and epidemiology.
Angiogenesis Inducing Agents ; Bronchopulmonary Dysplasia* ; Epidemiology ; Humans ; Infant, Newborn ; Infant, Premature ; Inflammation ; Lung ; Mortality ; Mothers ; Perfusion ; Placentation ; Pre-Eclampsia* ; Pregnancy ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1

Preeclampsia is a hypertensive disorder involving multiple organs during the late gestational period. It may cause maternal and fetal morbidity and mortality. Preeclampsia parturients have an increased risk of cesarean delivery for several reasons including growth retardation of the intrauterine fetus, fetal distress and termination of pregnancy for treatment of severe preeclampsia. The hemodynamic state of preeclampsia varies depending on the onset, the severity of preeclampsia and the involved organs. Spinal anesthesia is recommended for preeclampsia parturients because of its rapid onset, stable hemodynamics and fewer neurologic complications. Hypotension during spinal anesthesia occurs less in preeclampsia, as compared to healthy pregnant women. Hemodynamic monitoring and planned fluid administration are important to anesthetic management of preeclampsia parturients.
Anesthesia, Spinal ; Female ; Fetal Distress ; Fetus ; Hemodynamics* ; Humans ; Hypotension ; Mortality ; Pre-Eclampsia* ; Pregnancy ; Pregnant Women

Early injury to the lung circulation leads to the rapid development of pulmonary hypertension (PH) after premature birth. PH in bronchopulmonary dysplasia (BPD) results from increased vascular tone and abnormal vasoreactivity, hypertensive remodeling, and decreased vascular growth. The development of PH is sometimes a serious complication of BPD that can significantly impact the morbidity and mortality rates of preterm infants. Despite a gradual reduction in pulmonary arterial pressure postnatally, approximately a quarter of BPD infants have echocardiographic evidence of PH later. The pathogenesis of PH in BPD is very complex and multifactorial, often resulting from interactions between genetic and environmental or acquired factors (both prenatal and postnatal). Antenatal risk factors such as intrauterine growth retardation, maternal preeclampsia, and oligohydramnios suggest compelling evidence for the fetal origins of PH. Despite the potential importance of PH in preterm infants, the pathophysiology and the risk factors of PH in infants with BPD are still poorly understood. I have reviewed recent progress in research concerning the pathophysiology including the risk factors of PH in infants with BPD.
Arterial Pressure ; Bronchopulmonary Dysplasia* ; Echocardiography ; Female ; Fetal Growth Retardation ; Humans ; Hydrogen-Ion Concentration ; Hypertension, Pulmonary* ; Infant* ; Infant, Newborn ; Infant, Premature ; Lung ; Mortality ; Oligohydramnios ; Pre-Eclampsia ; Pregnancy ; Premature Birth ; Risk Factors*

BACKGROUND: Magnesium sulfate (MgSO4) is a drug of choice for women with preeclampsia, with evidence that it reduces progression to eclampsia and maternal mortality. However, no previous studies have been conducted on the effect of magnesium sulfate on labor. This retrospective study investigated the effect of magnesium sulfate on the labor duration and the neonatal outcomes in parturients with preeclampsia. METHODS: We reviewed the medical records of 209 women who delivered vaginally with the diagnosis of preeclampsia from January 1, 2003 to June 30, 2013. They were divided into two groups, primipara (Primi group) and multipara (Multi group). Then, each group was subclassified as MgSO4-treated (Mg group) and MgSO4-untreated group (Cont group) again. Collected data included the duration of each stage of labor and neonatal outcomes. RESULTS: The duration of the 1st stage of labor was significantly longer in the Multi-Mg group, compared with the Multi-Cont group (138 +/- 149 min vs. 88 +/- 92 min, P = 0.025). However, the total labor durations were comparable between the two groups. Primi group had no difference in durations of any stage of labor and the total duration. Neonates showed worse outcomes (lower birth weight, lower Apgar, higher NICU admission rate) in the Primi-Mg group than the Primi-Cont group. CONCLUSIONS: Although preeclamptic multiparous parturients treated with MgSO4 showed longer 1st stage of labor than those untreated with MgSO4, the total labor durations were comparable between the groups.
Diagnosis ; Eclampsia ; Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Magnesium Sulfate* ; Maternal Mortality ; Medical Records ; Pre-Eclampsia* ; Pregnancy ; Retrospective Studies

OBJECTIVES: With a gradual decline in maternal mortality in recent years in Iran, this study was conducted to identify the remaining risk factors for maternal death. METHODS: This 8-year nested case-control study was conducted in Hamadan Province, in the west of Iran, from April 2006 to March 2014. It included 185 women (37 cases and 148 controls). All maternal deaths that occurred during the study period were considered cases. For every case, four women with a live birth were selected as controls from the same area and date. Conditional logistic regression analysis was performed and the odds ratio (OR) and its 95% confidence interval (CI) were obtained for each risk factor. RESULTS: The majority of cases were aged 20-34 years, died in hospital, and lived in urban areas. The most common causes of death were bleeding, systemic disease, infection, and pre-eclampsia. The OR estimate of maternal death was 8.48 (95% CI=1.26-56.99) for advanced maternal age (> or =35 years); 2.10 (95% CI=0.07-65.43) for underweight and 10.99 (95% CI=1.65-73.22) for overweight or obese women compared to those with normal weight; 1.56 (95% CI=1.08-2.25) for every unit increase in gravidity compared to those with one gravidity; 1.73 (95% CI=0.34-8.88) for preterm labors compared to term labors; and 17.54 (95% CI= 2.71-113.42) for women with systemic diseases. CONCLUSIONS: According to our results, advanced maternal age, abnormal body mass index, multiple gravidity, preterm labor, and systemic disease were the main risk factors for maternal death. However, more evidence based on large cohort studies in different settings is required to confirm our results.
Body Mass Index ; Case-Control Studies* ; Cause of Death ; Cohort Studies ; Female ; Gravidity ; Hemorrhage ; Humans ; Iran* ; Live Birth ; Logistic Models ; Maternal Age ; Maternal Death ; Maternal Mortality* ; Obstetric Labor, Premature ; Odds Ratio ; Overweight ; Pre-Eclampsia ; Pregnancy ; Risk Factors* ; Thinness